The thyroid gland plays a vital role in controlling metabolic processes of the body. Under the control of the pituitary gland, it exerts its effects on various organs through the thyroid hormone. This hormone exists in two forms: 3,5,3'- triiodo - L - tyrosine (T.sub.3) and 3,5,3',5- tetraiodo - L - tyrosine (T.sub.4). Of these, T.sub.3 is more active as a hormone, but both function in a similar fashion to regulate cellular functions.
Most tissues have an absolute requirement for thyroid hormone for proper function and grave, potentially lethal, diseases result from both too low and too high thyroid hormone activity. Recent discoveries have provided new tools for the assessment of such diseases. While it has been known that the thyroid hormone exerts its effects on cells through receptors, the precise nature of the receptors has until recently, been unknown.
The cDNAs of a human thyroid receptor and a chicken thyroid receptor (erbA) have now been cloned and their amino acid sequences and the general structure of the receptors deduced from them shown to be related to those of previously known steroid hormone receptors. (Sap et al., Nature 324:635 (1986); Weinberger et al., Nature 324:641 (1986), both of which are incorporated herein by reference.) The steroid hormone receptors include those for glucorcorticoids (Miesfield et al., Cell 46:389 (1986); Danielsen et al., EMBO J. 5:2513 (1986), both of which are incorporated herein by reference) and estrogen (Kumar et al., EMBO J. 5:2231 (1986), which is incorporated herein by reference). It has been generally thought that there was only one thyroid receptor. Should others exist, their identification would be of importance in assessing thyroid function.
There thus exists a need to clone and identify other human erbA genes which may include further receptors binding the thyroid hormones in order to be able to accurately assess the functioning of the thyroid system in patients. The present invention satisfies these needs and provides related advantages as well.